Cells engaged in particle uptake become the center of inflammatory reactions. This is due, in part, to release from cells of substances previously sequestered within lysosomes. The studies proposed for the term of this project address themselves to the regulation of lysosomal enzyme release from human phagocytic cells and to the effect on purified proteoglycan species isolated from articular cartilage of lysosomal materials selectively extruded from leucocytes. The patterns will be determined of accumulation within or extrusion from phagocytic cells of cyclic nucleotides, prostaglandins and lysosomal enzymes. The physiological role of these compounds in modulation of enzyme release will be further studied by observing their response to agents which alter their synthesis or release. The extent of proteoglycan degradation caused by materials released from phagocytic cells will be estimated by changes in the chemical composition and physical properties (viscosity, sedimentation coefficient) of proteoglycan. An attempt will be made to isolate and characterize inhibitors of proteoglycan degradation naturally occurring in serum or synovial fluid from normal individuals and patients with rheumatoid arthritis.